What are the other Names for this Condition? (Also known as/Synonyms)

• Angel-shaped phalango-epiphyseal dysplasia
• ASPED

What is Angel-Shaped Phalangoepiphyseal Dysplasia? (Definition/Background Information)

• Angel-Shaped Phalangoepiphyseal Dysplasia (ASPED) is a form of acromelic dysplasia characterized by the distinctive radiological sign of angel-shaped middle phalanges, a typical metacarpophalangeal pattern profile (mainly affecting first metacarpals and middle phalanges of second, third and fifth digits, which all appear short), epiphyseal changes in the hips and, in some, abnormal dentition and delayed bone age
• Clinical manifestations in Angel-Shaped Phalangoepiphyseal Dysplasia are not only restricted to the hands, and the original description reported various combinations of angel-shaped middle phalanges, hip dysplasia and dental anomalies (hypodontia). Patients’ stature ranges from short to normal
• In addition, non-specific brachydactyly and hyperextensible interphalangeal joints have been reported, as well as delayed bone age
• Hip dysplasia gives rise to premature or severe osteoarthritis causing severe intermittent hip pain
• Delayed dentition, abnormally placed teeth, premature loss of teeth, abnormal enamel, and malocclusion have also been described in some

(Source: Angel-Shaped Phalangoepiphyseal Dysplasia; Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

Who gets Angel-Shaped Phalangoepiphyseal Dysplasia? (Age and Sex Distribution)

• Angel-Shaped Phalangoepiphyseal Dysplasia is a rare disease with less than 20 cases reported in the literature to date, however, it is likely underdiagnosed
• The exact prevalence of this disorder is unknown

(Source: Angel-Shaped Phalangoepiphyseal Dysplasia; Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

• Both males and females may be affected by Angel-Shaped Phalangoepiphyseal Dysplasia 

What are the Risk Factors for Angel-Shaped Phalangoepiphyseal Dysplasia? (Predisposing Factors)

• A positive family history may be an important risk factor, since Angel-Shaped Phalangoepiphyseal Dysplasia is an inherited condition

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Angel-Shaped Phalangoepiphyseal Dysplasia? (Etiology)

• Angel-Shaped Phalangoepiphyseal Dysplasia is caused by mutations in the growth differentiation factor 5 (GDF5) gene, located on chromosome 20q11.2, encoding CDMP1 (cartilage derived morphogenetic protein)
  • CDMP1 belongs to the TGF beta super family and plays a role in bone growth and joint morphogenesis
• The disorder is inherited in an autosomal dominant manner

(Source: Angel-Shaped Phalangoepiphyseal Dysplasia; Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

Autosomal dominant: Autosomal dominant conditions are traits or disorders that are present when only one copy of the mutation is inherited on a non-sex chromosome. In these types of conditions, the individual has one normal copy and one mutant copy of the gene. The abnormal gene dominates, masking the effects of the correctly function gene. If an individual has an autosomal dominant condition, the chance of passing the abnormal gene on to their offspring is 50%. Children, who do not inherit the abnormal gene, will not develop the condition or pass it on to their offspring

What are the Signs and Symptoms of Angel-Shaped Phalangoepiphyseal Dysplasia?

The signs and symptoms of Angel-Shaped Phalangoepiphyseal Dysplasia may vary, and include the following:

Very frequently present symptoms in 80-99% of the cases:

• Abnormality of epiphysis morphology
• Short 1st metacarpal
• Short middle phalanx of the 5th finger

Frequently present symptoms in 30-79% of the cases:

• Delayed eruption of teeth
• Hip dysplasia
• Hip osteoarthritis 
• Hypodontia

Occasionally present symptoms in 5-29% of the cases:

• Delayed skeletal maturation 
• Joint hyperflexibility

Other signs and symptoms include:

• Delayed ossification of carpal bones
• Hyperextensibility of the finger joints
• Premature osteoarthritis
• Pseudoepiphyses of the metacarpals

(Source: Angel-Shaped Phalangoepiphyseal Dysplasia; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How is Angel-Shaped Phalangoepiphyseal Dysplasia Diagnosed?

• The diagnostic methods for Angel-Shaped Phalangoepiphyseal Dysplasia include skeletal x-rays, showing the typical radiological features of the disorder, along with GDF5 molecular analysis, which confirms diagnosis
  • Angel-shaped middle phalanges are usually an isolated bone anomaly, and are shaped like ''Christmas tree angels'', with the wings formed by the diaphyseal cuff of bone surrounding the phalanx, the skirt by a cone-shaped epiphysis, and the head by the distal pseudoepiphysis
• As Angel-Shaped Phalangoepiphyseal Dysplasia is not a serious condition, prenatal diagnosis is not offered

(Source: Angel-Shaped Phalangoepiphyseal Dysplasia; Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Angel-Shaped Phalangoepiphyseal Dysplasia?

The complications of Angel-Shaped Phalangoepiphyseal Dysplasia may include:

• Premature or severe osteoarthritis
• Delayed dentition
• Abnormally placed teeth
• Premature loss of teeth
• Abnormal enamel
• Malocclusion (abnormal alignment of top and bottom rows of teeth)

(Source: Angel-Shaped Phalangoepiphyseal Dysplasia; Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

• Osteoarthritis can cause
  • Chronic pain
  • Reduced mobility
  • Development of obesity and heart disease due to reduced mobility

Complications may occur with or without treatment, and in some cases, due to treatment also

How is Angel-Shaped Phalangoepiphyseal Dysplasia Treated?

• The treatment for Angel-Shaped Phalangoepiphyseal Dysplasia may involve orthopedic management (i.e. hip arthroplasty), and plastic surgery (when thumb involvement is very severe or if syndactyly is associated). In patients with severe hip involvement, walking aids may be required
• For dental anomalies, orthodontic management may be necessary

(Source: Angel-Shaped Phalangoepiphyseal Dysplasia; Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

How can Angel-Shaped Phalangoepiphyseal Dysplasia be Prevented?

• Angel-Shaped Phalangoepiphyseal Dysplasia may not be preventable, since it is a genetic disorder
• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders
• Regular medical screening at periodic intervals with tests and physical examinations are recommended

What is the Prognosis of Angel-Shaped Phalangoepiphyseal Dysplasia? (Outcomes/Resolutions)

• Angel-Shaped Phalangoepiphyseal Dysplasia does not affect life-expectancy and the prognosis is good
• However, the quality of life is reduced in those with untreated and severe coxarthrosis

(Source: Angel-Shaped Phalangoepiphyseal Dysplasia; Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

Additional and Relevant Useful Information for Angel-Shaped Phalangoepiphyseal Dysplasia:

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/